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Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes

Nature Reviews Nephrology (2024)Cite this article

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Abstract

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD–PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patients at high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD–PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD–PH.

Key points

  • Pulmonary hypertension (PH) is common and independently associated with increased mortality in patients with chronic kidney disease or kidney failure; conversely, chronic kidney disease and kidney failure are common and independently associated with increased mortality in patients with PH.

  • In left-heart cardiorenal syndrome, impaired left ventricular function leads to pulmonary venous hypertension, which promotes pulmonary hypertension as well as renal dysfunction in the setting of renin–angiotensin–aldosterone system overactivation, salt avidity and hypervolaemia.

  • In right-heart cardiorenal syndrome, pulmonary arterial hypertension leads to severe pulmonary arterial remodelling, right-heart failure and impaired cardiac output, despite normal left-heart function. This process promotes kidney failure via neurohumoral, sympathetic and mechanical mechanisms.

  • Major overlap exists in the pathophysiology of pulmonary arterial remodelling and kidney failure, which could serve as the basis for potential therapeutic targets for both conditions.

  • No clear screening algorithms have been established for PH in kidney failure or kidney failure in PH.

  • PH could be a potential surrogate marker for risk of kidney failure, and opportunities may exist to improve outcomes by considering PH when determining the timing and appropriateness of kidney replacement therapy and/or kidney transplantation.

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Fig. 1: The classic pathophysiology of left-heart cardiorenal syndrome.
Fig. 2: The pathophysiology of pulmonary arterial hypertension (PAH), right-heart failure and cardiorenal syndrome.
Fig. 3: Imaging of the heart and kidneys to assess pulmonary hypertension and renal venous congestion in the setting of right-heart cardiorenal syndrome.
Fig. 4: Hemodynamic effects of an arteriovenous fistula and initiation of haemodialysis on the right and left heart.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Katarina Zeder

  2. Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

    Katarina Zeder & Gabor Kovacs

  3. Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Katarina Zeder & Bradley A. Maron

  4. Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    Katarina Zeder & Gabor Kovacs

  5. The University of Maryland-Institute for Health Computing, Bethesda, MD, USA

    Katarina Zeder & Bradley A. Maron

  6. Division of Nephrology and Hypertension, Vanderbilt Center for Kidney Disease and Integrated Program for Acute Kidney Injury, Nashville, TN, USA

    Edward D. Siew

  7. Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Evan L. Brittain

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Contributions

K.Z., E.D.S. and B.A.M. researched the data for the article. K.Z. and B.A.M. wrote the manuscript. All authors made substantial contributions to discussions of the content and reviewed or edited the manuscript before submission.

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Correspondence to Bradley A. Maron.

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Nature Reviews Nephrology thanks Daniel Edmonston, Faeq Husain-Syed, who co-reviewed with Khodr Tello, and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Supplementary information

Glossary

Backward congestion

In right-heart failure, the right ventricle is unable to pump sufficient blood into the pulmonary arteries. Thus, blood pools in the systemic veins, leading to increased volume and pressure.

Cardiac index

A haemodynamic parameter that relays the blood flow (measured in litres per minute) from the left ventricle to the body surface area and provides a measure of heart performance in relation to the body size of the individual.

E/E′ ratio

An echocardiographic measure for the diastolic function of the left ventricle.

Plexogenic vasculopathy

Vascular changes of the small pulmonary arteries in patients with pulmonary arterial hypertension, predominated by arterial medial hypertrophy, intimal proliferation and development of plexiform lesions

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Zeder, K., Siew, E.D., Kovacs, G. et al. Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes. Nat Rev Nephrol (2024). https://doi.org/10.1038/s41581-024-00857-7

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